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Biomedical subjects

L Mantelli

Publications and source records attributed to L Mantelli.

At least 37 records · Page 2Linked to original sources
PubMed1991

Adenosine receptors involved in the inhibitory control of non-adrenergic non-cholinergic neurotransmission in guinea-pig atria belong to the A1 subtype.

We have previously shown that endogenous adenosine inhibits non-adrenergic, non-cholinergic (NANC) neurotransmission in isolated guinea-pig atria. In the present study the effect of adenosine analogues, such as N6 cyclopentyladenosine (CPA), 5' N-ethylcarboxamide adenosine (NECA), 2 chloroadenosine (2-CADO), R- and S-phenylisopropyladenosine (R- and S-PIA) on the cardiac response to transmural nerve stimulation has been tested in order to characterize the subtype of adenosine receptor involved in the inhibitory control of NANC neurotransmission. The effect of the adenosine antagonist 8-phenyltheophylline (8-PT) was then tested against CPA and NECA. The prototypical A-1 selective agonist CPA was the most active agonist, reducing the response to the stimulation of NANC nerves with an IC50 value of 2.8 nM; R-PIA, NECA and 2-CADO showed IC50 values of 9.5, 13.7 and 35 nM respectively. S-PIA was the least active agonist, showing an IC50 value (306 nM) about 30-fold greater than that of R-PIA (9.5 nM). None of the agonists tested was able to modify cardiac response to exogenous CGRP. Furthermore, 8-PT competitively antagonized the effect of CPA and NECA with very close pA2 values (6.77 +/- 0.01 and 6.63 +/- 0.08 respectively). From these findings we concluded that prejunctional inhibitory adenosine receptors on capsaicin sensitive sensory nerves of cardiac tissue belong to the A-1 subtype.

2-Chloroadenosine↗
PubMed1991

Modulation by adrenergic transmitters of the efferent function of capsaicin-sensitive nerves in cardiac tissue.

In atrial preparations obtained from reserpine-pre-treated guinea-pigs, incubated in the presence of 1 microM atropine plus 1 microM CGP 20712A (a beta 1 blocking drug), a positive inotropic effect due to CGRP release from capsaicin-sensitive sensory neurons was induced by electrical field stimulation (EFS). This response was concentration-dependently reduced by noradrenaline (0.01-3 microM), neuropeptide Y (NPY, 3-300 nM) and adenosine triphosphate (ATP, 1-30 microM). On the other hand, the overflow of [3H]-noradrenaline from sympathetic nerve terminals induced by EFS in isolated atria obtained from normal untreated animals was not modified in 10 nM calcitonin gene-related peptide (CGRP). Substance P (SP) and neurokinin A (NKA), at concentrations ranging from 0.01 to 1 microM did not affect the cardiac response to field stimulation of adrenergic terminals of atrial tissue. These findings demonstrate that all the co-transmitters stored in adrenergic nerve terminals have a modulatory role on the efferent function of cardiac capsaicin-sensitive sensory neurons, while cardiac adrenergic neurotransmission is not influenced by the peptidergic transmitters released from sensory neurons.

Adenosine Triphosphate↗
PubMed1991

Prejunctional prostanoid receptors on cardiac adrenergic terminals belong to the EP3 subtype.

1. The effects of prostaglandin E2 (PGE2) and of several synthetic prostanoids on the cardiac response to sympathetic nerve stimulation in guinea-pig atria have been evaluated. 2. PGE2 (0.01-100 nM), sulprostone (0.01-100 nM) and misoprostol (0.1-100 nM), but not butaprost (0.1-100 nM), dose-dependently reduced the increase in cardiac contractility induced by electrical field stimulation of sympathetic terminals. 3. The EP1 antagonist AH6809 (1 microM) did not modify the inhibition of cardiac response induced by PGE2, sulprostone and misoprostol. 4. In preparations preloaded with [3H]-noradrenaline, tritium overflow induced by electrical field stimulation was greatly and significantly reduced by 100 nM PGE2 and by 100 nM sulprostone. 5. These results indicate that PGE2 and other synthetic prostanoids reduce noradrenaline release from cardiac adrenergic nerve terminals acting on prejunctional inhibitory receptors belonging to the EP3 subtype.

Animals↗
PubMed1990

Characterization of opioid receptors modulating the function of capsaicin-sensitive neurons in guinea-pig atria.

Transmural nerve stimulation of isolated atria, obtained from reserpine-pretreated guinea-pigs, in the presence of atropine and the beta 1-adrenoceptor-blocking drug CGP 20712A, induced a positive inotropic effect. [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO), [D-Ala2,D-Leu5]enkephalin (DADLE), morphine and dynorphin dose dependently reduced the cardiac response to transmural nerve stimulation. The delta receptor selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE), and the kappa receptor agonist, U50488, were unable modify the response. The inhibitory effect of all the active opioid agonists was antagonized by naloxone but not by the selective delta and kappa opioid receptor antagonists, ICI 174.864 and MR 2266. These results suggest the presence on sensory nerve terminals of inhibitory opioid receptors belonging to the mu, but not to the delta and kappa subtypes.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Adenosine modulation of non-adrenergic non-cholinergic neurotransmission in isolated guinea-pig atria.

Transmural stimulation of non-adrenergic, non-cholinergic sensory nerves in guinea-pig atria, isolated from reserpine-pretreated animals, in the presence of atropine and the beta-adrenoceptor-blocking drug CGP 20712A, induced a positive inotropic effect. Adenosine (0.1-10 microM) concentration-dependently reduced the cardiac response to transmural nerve stimulation, without modifying the response to exogenous calcitonin gene-related peptide; the inhibitory effect of adenosine was antagonized by 1 microM 8-phenyltheophylline. Moreover, the cardiac response to field stimulation was enhanced by 8-phenyltheophylline (0.1, 1 microM) and by adenosine deaminase (1 microgram/ml), but was reduced by dipyridamole (1 microM). These findings indicate the presence of inhibitory adenosine receptors on cardiac sensory nerves and suggest a modulatory effect of endogenous adenosine on cardiac non-adrenergic, non-cholinergic neurotransmission.

Adenosine↗
PubMed1990

Different effects of prostaglandins on adrenergic neurotransmission in atrial and ventricular preparations.

1. The effects of prostaglandin E2 (PGE2) and iloprost on the cardiac response to adrenergic nerve stimulation in guinea-pig atrial and ventricular preparations have been studied. 2. In guinea-pig isolated atria both PGE2 (0.1-10 nM) and iloprost (0.1-3 microM) concentration-dependently reduced the cardiac response to adrenergic nerve stimulation. 3. The inhibition of cyclo-oxygenase by indomethacin and acetylsalicylic acid potentiated the response to nerve stimulation in the atrial preparations. 4. Arachidonic acid (1-10 microM) reduced the response to nerve stimulation in atria. This effect was prevented by indomethacin and acetylsalicylic acid. 5. In guinea-pig ventricles PGE2 and iloprost were found to be effective at higher concentrations than in atrial preparations: arachidonic acid, indomethacin or acetylsalicylic acid did not modify the cardiac response to adrenergic nerve stimulation. 6. These results suggest a different modulator role for endogenous prostaglandins in atrial and ventricular tissue.

Animals↗
PubMed1989

Effects of opioid drugs on capsaicin-sensitive neurones in guinea-pig atria.

Transmural nerve stimulation of isolated guinea-pig atria in the presence of atropine induced a biphasic positive inotropic effect but only a slow increase in contractility (NANC response) in atria obtained from 6-hydroxy-dopamine-pretreated animals. The latter effect disappeared after exposure of the preparations to capsaicin. The effects of some opioid peptides were investigated on NANC responses. [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.1-10 microM) inhibited the cardiac response to transmural nerve stimulation in a dose-dependent and naloxone-sensitive manner. Dynorphin-(1-13) and morphine, at 10-fold higher concentrations (1-10 microM), reduced the response in a naloxone-sensitive manner. Naloxone alone however did not affect the response. Opioid peptides were not able to reduce the positive inotropic effect induced by calcitonin gene-related peptide (CGRP), or the increase in cardiac contractility produced by capsaicin. These results suggest that opioid receptors exert a modulatory role on peripheral terminals of capsaicin-sensitive sensory nerves.

Animals↗
PubMed1989

Indirect evidence for a role of prostaglandins as second messengers of the prejunctional effect of opioids in guinea-pig ventricular preparations.

The cardiac response to adrenergic nerve stimulation was dose dependently reduced in a statistically significant manner by 1-10 microM dynorphin-(1-13) in isolated atria, and by 0.1-1 microM dynorphin-(1-13) in guinea-pig ventricular preparations. The inhibitory effect of dynorphin was maintained in atria that had been pretreated with two cyclooxygenase inhibitors at concentrations that induce an 80% inhibition of the enzyme, namely indomethacin 3 microM and acetylsalicylic acid 200 microM. The inhibitory effect of dynorphin disappeared in similarly pretreated ventricular preparations. These results suggest that, whilst the mediation of the effect of dynorphin is carried out mainly by specific opioid receptors in the atrial section, in the ventricular tissue it occurs through the endogenous prostanoid system.

Animals↗
PubMed1989

Effect of lithium chloride on the neurotransmitter release from adrenergic nerve terminals of guinea-pig atria.

Lithium chloride at 1 and 10 mM produced a dose-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals, without affecting myocardial contractility in electrically stimulated guinea-pig atria. This effect was calcium-independent and was also present in preparations superfused with 10 mM myoinositol. Moreover, 10 mM lithium chloride reduced the positive inotropic effect of tyramine. These results indicate that lithium reduces the evoked release of noradrenaline from the adrenergic nerve endings, probably lowering the content of releasable neurotransmitter.

Animals↗
PubMed1988

Influence of lithium on the positive inotropic effect of phenylephrine and isoprenaline in guinea-pig heart.

The influence of lithium on the positive inotropic effects mediated by alpha- and beta-adrenoceptor stimulation was studied in isolated guinea-pig ventricular preparations stimulated at 1 Hz. Lithium chloride (10(-3)-2 X 10(-2) M) shifted the concentration-response curve for the inotropic effect of phenylephrine to the right in a dose-dependent manner. [3H]Prazosin binding was not inhibited by 10(-2) M lithium. The antagonistic effect of lithium was almost completely prevented by the presence of 10(-2) M myoinositol, and was potentiated by 10(-4) M 2-2'-anhydro-2-C-(hydroxymethyl)-myo-inositol, an antagonist of myo-inositol. The positive inotropic effect of isoprenaline was completely unaffected by either 10(-2) M lithium, 10(-2) M myo-inositol, or 10(-4) M 2-2'-anhydro-2-C-(hydroxymethyl)-myo-inositol. Since it is known that lithium interferes with inositol phosphate metabolism, our results produce further indirect evidence of an involvement of inositol phosphates in the myocardial response to alpha-adrenoceptor, but not to beta-adrenoceptor, stimulation. Our findings also suggest that chronic lithium treatment could interfere with the adrenergic modulation of myocardial contractility in those physio-pathological conditions in which the role of myocardial alpha-adrenoceptors becomes predominant.

Animals↗
PubMed1988

Indirect evidence for a role of phosphatidylinositol turnover in the cardiac response to H1-receptor stimulation.

The influence of lithium on the positive inotropic effect of the H1-agonist 2-pyridyl-ethylamine (PEA) and of the H2-receptor agonist 4-methylhistamine was studied in isolated guinea-pig ventricular strips electrically stimulated at 1 Hz. Lithium (1-10 mM) was devoid of any effect on cardiac contraction; the positive inotropic effect of 4-methylhistamine was unaffected in the presence of 10 mM lithium. On the other hand, lithium (1-10 mM) dose-dependently shifted the dose-inotropic effect curve for PEA to the right; an antagonistic effect, qualitatively similar to that of lithium, was induced by the myoinositol antagonist 2-2'-anhydro-2-C-hydroxymethyl-myoinositol, at a concentration of 100 microM. Moreover the antagonistic effect of the higher lithium concentration (10 mM) was almost completely prevented in preparations superfused with 10 mM myoinositol. Since it is known that lithium is able to reduce the cellular availability of myoinositol by an interference with the phosphatidylinositol (PI) cycle, these results suggest that the H1-receptor-mediated increase in contractility may be linked to an increased turnover of PI, while the H2-receptor-mediated one is not.

Animals↗
PubMed1987

On the presence of opioid receptors in guinea-pig ventricular tissue.

The cardiac response to sympathetic nerve stimulation, induced by trains of field pulses, was studied in isolated guinea-pig ventricular strips. Dynorphin-(1-13) and [D-Ala2, D-Leu5]enkephalinamide, but not morphine, reduced, in a dose-dependent manner, the cardiac sympathetic response. The effect of the two opioid peptides was antagonized by naloxone. The opioid agonists did not affect the response to exogenous noradrenaline. Neither naloxone nor a mixture of peptidase inhibitors modified the cardiac response to sympathetic nerve stimulation.

Animals↗
PubMed1987

Development of tolerance to effects of morphine on cardiac sympathetic response.

1. In isolated guinea-pig atria, morphine potentiated the response to sympathetic stimulation in a naloxone-insensitive, but calcium-sensitive way. The potentiating effect of morphine disappeared in the presence of desmethylimipramine; moreover morphine enhanced the dose-effect curve for exogenous noradrenaline. 2. Morphine was ineffective in guinea-pig atria obtained from animals implanted with morphine pellets for 4 days; on the other hand DADLE and dynorphin-(1-13) maintained their usual inhibitory effect on cardiac sympathetic response in the same kind of preparation. 3. In atria obtained from morphine-tolerant animals and maintained in vitro in the presence of morphine, removal of morphine from the bathing solution caused a new potentiating effect.

Animals↗